Phosphonopeptides as Antibacterial Agents: Alaphosphin and Related Phosphonopeptides

摘要: Alaphosphin, l-alanyl-l-1-aminoethylphosphonic acid, was selected from a range of phosphonopeptides for evaluation in humans on the basis its antibacterial activity, pharmacokinetics, and stability to intestinal kidney peptidases. In vitro, action antagonized by small peptides, resulting low activity peptone media. On an antagonist-free medium alaphosphin bactericidal rapidly lysed most susceptible gram-negative bacteria, but it largely bacteriostatic essentially nonlytic against gram-positive organisms. Its spectrum included strains normally isolated urinary tract infections, potency greatly reduced very high inoculum levels alkaline pH. Although Proteus Pseudomonas were less than other common like species they formed spheroplasts when exposed under appropriate conditions. Alaphosphin equally effective penicillin-susceptible -resistant showed no cross-resistance with known antibiotics. Good synergy increased demonstrated combinations d-cycloserine or β-lactam Images